The added value of ultrasound imaging biomarkers to clinicopathological factors for the prediction of high-risk Oncotype DX recurrence scores in patients with breast cancer.

Background: The Oncotype DX (ODX) recurrence score (RS), a 21-gene assay, has been proven to recognize patients at high risk of recurrence (RS ≥26) who would benefit from chemotherapy. However, it has limited availability and high costs. Our study thus aimed to identify ultrasound (US) imaging biomarkers and develop a prediction model for identifying patients with a high ODX RS. Methods: In this retrospective study, consecutive patients with T1-3N0-1M0 breast cancer who were hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative who had an available ODX RS were reviewed. Patients treated from May 2012 and December 2015 were placed into a training cohort, and those treated from January 2016 to January 2017 were placed in a validation cohort. Clinicopathologic data were collected, and preoperative US scans were analyzed. Univariable and multivariable regression analyses were performed to evaluate the independent predictors for a high-risk of breast cancer in the training cohort, and a nomogram was developed and evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: A total of 363 patients were in the training cohort and 160 in the validation cohort, with the proportion with a high RS (RS 26-100) being 14% and 13.1%, respectively. Echogenic halo, enhanced posterior echo, low level of progesterone receptor (PR), and high Ki-67 index were identified as independent risk factors for high RS (all P values <0.05). The nomogram was constructed based on the combined model, which showed a better discrimination ability than did the clinicopathological model [combined model: AUC =0.95, 95% confidence interval (CI): 0.93-0.97; clinicopathological model: AUC =0.89, 95% CI: 0.86-0.92; P=0.001] and greater clinical benefit according to DCA. Furthermore, the nomogram was found to be effective in the validation cohort (AUC =0.90, 95% CI: 0.84-0.94), especially in patients with stage T1N0M0 disease (AUC =0.91, 95% CI: 0.84-0.95). Conclusions: US features may serve as valuable imaging biomarkers for the prediction of high recurrence risk in patients with T1-3N0-1M0 breast cancer and hormone receptor (HR)-positive and HER2-negative status. A nomogram incorporating PR status, Ki-67 index, and US imaging biomarkers showed a good discrimination ability in the early selection of patients at high risk of recurrence, especially in those with stage T1N0M0 disease.

Predicting three or more metastatic nodes using contrast-enhanced lymphatic US findings in early breast cancer.

OBJECTIVES: To develop and validate a nomogram for predicting ≥ 3 metastatic axillary lymph nodes (ALNs) in early breast cancer with no palpable axillary adenopathy by clinicopathologic data, contrast-enhanced (CE) lymphatic ultrasound (US), and grayscale findings of sentinel lymph nodes (SLNs). MATERIALS AND METHODS: Women with T1-2N0 invasive breast cancer were consecutively recruited for the CE lymphatic US. Patients from Center 1 were grouped into development and internal validation cohorts at a ratio of 2:1. The external validation cohort was constructed from Center 2. The clinicopathologic data and US findings of SLNs were analyzed. A nomogram was developed to predict women with ≥ 3 metastatic ALNs. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curve analysis. RESULTS: One hundred seventy-nine from Center 1 were considered the development cohorts. The remaining 90 participants from Center 1 were internal cohorts and 197 participants from Center 2 were external validation cohorts. The US findings of no enhancement (odds ratio (OR), 15.3; p = 0.01), diffuse (OR, 19.1; p = 0.01) or focal eccentric (OR, 27.7; p = 0.003) cortical thickening, and absent hilum (OR, 169.7; p < 0.001) were independently associated with ≥ 3 metastatic ALNs. Compared to grayscale US or CE lymphatic US alone, the nomogram showed the highest AUC of 0.88 (0.85, 0.91). The nomogram showed a calibration slope of 1.0 (p = 0.80-0.81; Brier = 0.066-0.067) in validation cohorts in predicting ≥ 3 metastatic ALNs. CONCLUSION: Patients likely to have ≥ 3 metastatic ALNs were identified by combining the lymphatic and grayscale US findings of SLNs. Our nomogram could aid in multidisciplinary treatment decision-making. TRIAL REGISTRATION: This trial is registered on www.chictr.org.cn : ChiCTR2000031231. Registered March 25, 2020. CRITICAL RELEVANCE STATEMENT: A nomogram combining lymphatic CEUS and grayscale US findings of SLNs could identify early breast cancer patients with low or high axillary tumor burden preoperatively, which is more applicable to the Z0011 era. Our nomogram could be useful in aiding multidisciplinary treatment decision-making for patients with early breast cancer. KEY POINTS: • CEUS can help identify and diagnose SLN in early breast cancer preoperatively. • Combining lymphatic and grayscale US findings can predict axillary tumor burden. • The nomogram showed a high diagnostic value in validation cohorts.

Deep learning-based system for automatic prediction of triple-negative breast cancer from ultrasound images.

To develop a deep-learning system for the automatic identification of triple-negative breast cancer (TNBC) solely from ultrasound images. A total of 145 patients and 831 images were retrospectively enrolled at Peking Union College Hospital from April 2018 to March 2019. Ultrasound images and clinical information were collected accordingly. Molecular subtypes were determined from immunohistochemical (IHC) results. A CNN with VGG-based architecture was then used to predict TNBC. The model's performance was evaluated using randomized k-fold stratified cross-validation. A t-SNE analysis and saliency maps were used for model visualization. TNBC was identified in 16 of 145 (11.03%) patients. One hundred fifteen (80%) patients, 15 (10%) patients, and 15 (10%) patients formed the train, validation, and test set respectively. The deep learning system exhibits good efficacy, with an AUC of 0.86 (95% CI: 0.64, 0.95), an accuracy of 85%, a sensitivity of 86%, a specificity of 86%, and an F1-score of 0.74. In addition, the internal representation features learned by the model showed clear differentiation across molecular subtype groups. Such a deep learning system can automatically predict triple-negative breast cancer preoperatively and accurately. It may help to get to more precise and comprehensive management.

Contrast-enhanced lymphatic US can improve the preoperative diagnostic performance for sentinel lymph nodes in early breast cancer.

OBJECTIVES: To evaluate the preoperative diagnostic value of contrast-enhanced lymphatic ultrasound (CEUS) for the sentinel lymph node (SLN) status in early breast cancer. MATERIALS AND METHODS: We prospectively recruited 102 consecutive patients with clinically node-negative early breast cancer from July 2021 to October 2021. All patients underwent conventional US and percutaneous CEUS examinations. The CEUS of SLNs were classified into four enhancement patterns: homogeneous (I), featured inhomogeneous (II), focal defect (III), and no enhancement (IV). The diagnostic performance of conventional US and CEUS for SLN metastasis was assessed by receiver operating characteristic (ROC) curves and decision curves. RESULTS: A total of 78 women were enrolled in this study, including 55, 18, and 5 patients with negative axilla, 1-2, and ≥ 3 metastastic SLNs pathologically, respectively. The identification rate of SLNs by CEUS was 100%. Patterns I and II can select 91.7% (44/48) of patients with disease-free axilla, while patterns III and IV had higher percentages of metastasis (65.2%, p < 0.001 and 57.1%, p < 0.002, respectively). For the SLN metastatic burden, 100% (48/48) of patients with pattern I/II had ≤ 2 metastatic SLNs. Compared with conventional US, the CEUS enhancement patterns showed significant improvement in diagnosing metastatic SLNs (0.813 vs 0.601, p < 0.001). CEUS had greater clinical benefits and correctly reclassified 48% of metastatic SLNs (p < 0.001) without sacrificing the classification accuracy of negative SLNs (p = 0.25), and could improve prediction accuracy by 0.42 (p < 0.001). CONCLUSIONS: CEUS demonstrated better diagnostic performance and greater clinical benefits than conventional US for the preoperative diagnosis of SLNs, showing its potential to select candidates for precluding axillary surgery in early breast cancer. KEY POINTS: • The homogeneous and featured inhomogeneous enhancement of SLNs are highly suggestive of negative LNs, while focal defect (p < 0.001) and no enhancement (p < 0.002) patterns had higher percentages of metastasis. • The proportion of SLNs with highly suspicious signs on conventional US increases as the type of enhancement pattern increases (no suspicious signs in pattern I/II, 34.8% in pattern III, and 85.7% in pattern IV). • Compared with conventional US, CEUS improved the area under the receiver operating characteristic curve (0.813 vs. 0.601, p < 0.001) and had greater clinical benefits (IDI = 0.42, p < 0.001) for the diagnosis of axillary metastasis.

A Full Range Experimental Study of Amplitude- and Frequency-Dependent Characteristics of Rubber Springs.

This paper provides a comprehensive understanding of the amplitude- and frequency-dependent characteristics of rubber springs. The dynamic nonlinear inelasticity of rubber is a key academic problem for continuum mechanics and a bottleneck problem for the practical use of rubber structures. Despite intensive efforts witnessed in industrial applications, it still demands an unambiguous constitutive model for dynamic nonlinear inelasticity, which is known as the Payne effect. To this end, three types of rubber springs (shear-type (ST), compression-type (CT) and shear-compression-combination-type (SCCT)) were tested with amplitude and frequency sweeps in different conditions. We investigated and present changes in dynamic stiffness and loss factor with amplitude, frequency and the hysteresis loops of different rubber springs. We also propose a hypothesis and research strategy to study a constitutive model involving multiple factors of hyperelasticity, the Mullins effect, viscoelasticity and the Payne effect, which we hope will provide new ideas for the establishment of a constitutive equation.

Value of high-frequency ultrasound in the treatment of moderate and severe acne vulgaris.

BACKGROUND: Acne treatment may fail or cause undesirable side effects due to inaccurate evaluation. High-frequency ultrasound (HFUS) can monitor systemic treatment in patients with moderate-to-severe acne vulgaris. MATERIALS AND METHODS: In this prospective study, consecutive patients with moderate-to-severe acne vulgaris were recruited. Patients were graded by a comprehensive clinical assessment before and after therapy. Simultaneous HFUS grading was independently evaluated according to the sonographic scoring system for acne (SSSA). Clinical and HFUS grades were compared through kappa analysis. RESULTS: A total of 70 patients were enrolled. At baseline, 36 (51.4%) and 34 (48.6%) patients were graded as moderate and severe, respectively, through clinical assessment. However, 27 patients (38.6%) scored SSSA-Grade II and 43 (61.4%) scored SSSA-Grade III in the HFUS grading. Sixty-one patients (87.1%) were in the consistent category as per clinical assessment and HFUS grades, with Kappa1  = 0.745, whereas higher HFUS grades were observed in nine patients. By the end of the observation, 65 of all patients (92.9%) showed significant improvement and 5 (7.1%) showed no apparent improvement after the treatment. According to the clinical assessment, 14, 52, and 4 patients were graded as mild, moderate, and severe, respectively. On the other hand, 11, 51, and 8 patients had SSSA-Grade I, II, and III, respectively. Of all patients, 63 (90.0%) had consistent evaluation results, with Kappa2  = 0.762, whereas the remaining seven patients had an HFUS grade higher than the clinical. CONCLUSION: HFUS is a useful tool for dermatologists to monitor the treatment of moderate and severe acne vulgaris.

A comparative study of melanocytic nevi classification with dermoscopy and high-frequency ultrasound.

BACKGROUND: Melanocytic nevi (MN) can be classified into three subtypes according to the depth of the nests of nevus cells which is important for management. High-frequency ultrasound (HF-US) can clearly reveal the lesion size, contour, depth, and internal structures. However, the HF-US studies of MN according to subtypes are limited. We aimed to describe the HF-US features of MN and explore its value in accurate classification. MATERIALS AND METHODS: This retrospective study was conducted from January 2018 to November 2019. Eighty-five patients with MN were included and examined by 50 and 20 MHz HF-US. The HF-US features were recorded including morphological flatness, depth, shape, boundary, internal echogenicity, hyperechoic spots, lateral acoustic shadow, posterior echoic patterns, mushroom signs, and straw-hat signs. Each image was evaluated by two physicians independently, and the consistency was tested. RESULTS: Eleven lesions could not be detected by HF-US. The rest 74 lesions underwent ultrasonic analysis. MN appeared as strip-shaped or oval, hypoechoic areas localized in the epidermis and dermis under ultrasonography. A strong consistency between HF-US and dermoscopy of determining the lesion depth was achieved (κ = 0.935, p < 0.001). The hyperechoic spots were found in 57.6% intradermal nevi. The mushroom signs were seen in 34.8% intradermal nevi, and the straw-hat signs were seen in all the compound nevi. CONCLUSION: MN can be correctly classified using HF-US, and it had a strong correlation with dermoscopic and clinical classification. HF-US could further reveal the internal morphological features of MN, which may support more precise classification and management.

Usefulness of high-frequency ultrasound in differentiating basal cell carcinoma from common benign pigmented skin tumors.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy. Occasionally, it may have an appearance similar to that of some benign pigmented skin lesions. Therefore, additional information is needed to differentiate these lesions. MATERIALS AND METHODS: A diagnostic accuracy study was performed from February 2018 to April 2019. All lesions underwent ultrasound examination with 50 and 20 MHz probes. The high-frequency ultrasound (HFUS) images were evaluated independently by 2 experienced doctors for the presence of predefined features, including the depth, shape, margin, anechoic area, hyperechoic spots, epidermal interrupted echo, mushroom sign, flat-bottom sign, and superficial hyperechoic focus (SHEF). RESULTS: A total of 54 BCCs, 51 melanocytic nevi and 55 seborrheic keratoses (SK), were included. BCCs often involved the subcutaneous tissue (11/54, 20.4%; P < .001) and had an irregular shape (26/54, 48.1%; P < .001) and ill-defined borders (26/54, 48.1%; P < .001), while most benign pigmented lesions had a regular shape (101/106, 95.3%; P < .001) and well-defined borders (95/106, 89.6%; P < .001). BCCs occasionally showed anechoic areas (10/54, 18.5%; P < .001) and epidermal interrupted echo (18/54, 33.3%; P < .001). Moreover, hyperechoic spots could be found in BCCs (43/54, 79.6%), nevi (27/51, 52.9%), and SK (30, 54.5%) (P = .001), with mean number of 7.3, 5.5, and 8.0, respectively. The mushroom signs were all present in melanocytic nevi (18/51, 35.3%), while the flat-bottom sign (43/55, 78.2%; P < .001) and SHEF (40/55, 72.7%; P < .001) presented mainly in SKs. CONCLUSIONS: Based on the typical features, HFUS could improve the accuracy of BCC identification and should be considered when dermatologists are unsure about the lesion type.

Nomogram based on radiomics analysis of primary breast cancer ultrasound images: prediction of axillary lymph node tumor burden in patients.

OBJECTIVES: To establish a prediction model for evaluating the axillary lymph node (ALN) status of patients with T1/T2 invasive breast cancer based on radiomics analysis of US images of primary breast lesions. METHODS: Between August 2016 and November 2018, a total of 343 patients with histologically proven malignant breast tumors were included in this study and randomly assigned to the training and validation groups at a ratio of 7:3. ALN tumor burden was defined as low (< 3 metastatic ALNs) or high (≥ 3 metastatic ALNs). Radiomics features were obtained using the PyRadiomics package, and the radiomics score was established by least absolute shrinkage and selection operator regression. A nomogram combining the breast cancer US radiomics score with patient age and lesion size was generated based on the multivariate logistic regression results. RESULTS: In the training and validation cohorts, 29.1% (69/237) and 32.08% (34/106) of patients were pathologically diagnosed with more than 2 metastatic ALNs, respectively. The radiomics score consisted of 16 US features, and patient age and lesion diameter identified by US were included to construct the model. The AUC of the model was 0.846 (95% CI, 0.790-0.902) for the training cohort and 0.733 (95% CI, 0.613-0.852) for the validation cohort. The calibration curves showed good agreement between the predictions and observations. CONCLUSIONS: Our novel nomogram demonstrates high accuracy in predicting ALN tumor burden in breast cancer patients. We also suggest further development of PyRadiomics to improve US radiomics. KEY POINTS: • A nomogram based on US was developed to predict ALN tumor burden (low, < 3 metastatic ALNs; high, ≥ 3 metastatic ALNs). • The nomogram could assist clinicians in evaluating treatment strategies for T1/T2 invasive breast cancer.

Predicting Axillary Lymph Node Status With a Nomogram Based on Breast Lesion Ultrasound Features: Performance in N1 Breast Cancer Patients.

OBJECTIVE: To develop a nomogram for predicting axillary lymph node (ALN) metastases using the breast imaging reporting and data system (BI-RADS) ultrasound lexicon. METHODS: A total of 703 patients from July 2015 to January 2018 were included in this study as a primary cohort for model construction. Moreover, 109 patients including 51 pathologically confirmed N1 patients (TNM staging) and 58 non-metastatic patients were recruited as an external validation cohort from March 2018 to August 2019. Ultrasound images and clinical information of these patients were retrospectively reviewed. The ultrasonic features based on the BI-RADS lexicon were extracted by two radiologists. The features extracted from the primary cohort were used to develop a nomogram using multivariate analysis. Internal and external validations were performed to evaluate the predictive efficacy of the nomogram. RESULTS: The nomogram was based on two features (size, lesion boundary) and showed an area under the curve of 0.75 (95% confidence interval [CI], 0.70-0.79) in the primary cohort and 0.91 (95% CI, 0.84-0.97) in the external validation cohort; it achieved an 88% sensitivity in N1 patients. CONCLUSION: The nomogram based on BI-RADS ultrasonic features can predict breast cancer ALN status with relatively high accuracy. It has potential clinical value in improving the sensitivity and accuracy of the preoperative diagnosis of ALN metastases, especially for N1 patients.

Diagnostic value of pelvic floor ultrasonography for diagnosis of pelvic organ prolapse: a systematic review.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) is a common medical condition universally. In addition to physical examination, experts have increasingly turned their attention to ultrasound in diagnosing POP for its low cost and dynamic imaging. The aim of this paper is to provide an overview of the methods of pelvic floor ultrasound in diagnosing POP, which has been lacking up till now. METHODS: We included original papers comparing the outcome of the Pelvic Organ Prolapse Quantification system and ultrasound, published from 2008 to present in English, using electronic databases (MEDLINE, EMBASE, CENTRAL, PUBMED). All stages of the review were conducted in parallel by two reviewers. RESULTS: Fifteen papers were included. We found that current methods have advantages and limitations. The main methods are to measure levator hiatus-related parameters and distances between the lowest point of the pelvic organs and reference lines during Valsalva maneuver, contraction, and at rest. CONCLUSIONS: Pelvic floor ultrasound is valuable in diagnosing POP, yet suffers from a weakness in precision compared with physical examination. From the existing research, we found that the differences in baseline data such as weight, height, ethnicity, etc., may affect the cutoffs of the above-mentioned parameters. Further research is required to find one appropriate cutoff for each parameter, even if it is necessary to set group values for every parameter according to varying situations.

Efficiency and safety of TachoSil® in the treatment of postoperative air leakage following pulmonary surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: There has been still no consensus whether to apply TachoSil® to reduce the incidence of air leakage after pulmonary surgery. We conducted this meta-analysis of randomized controlled trials (RCTs) to identify the efficiency and safety of TachoSil® applied in the prevention of postoperative air leakage following pulmonary surgery. METHODS: We performed a systematic electronic search through EMABSE, PubMed and Web of Science up to March 2018. Summary risk ratio (RR) and weight mean difference (WMD) with corresponding 95% confidence intervals (CI) were calculated to analyze the outcomes. Fixed effect or random effect model was used to pool the estimates. Two independent reviewers assessed the quality of included studies using Cochrane risk-of-bias tool for RCTs. RESULTS: We included six RCTs with a total of 921 patients. Compared with standard treatment (suturing, stapling techniques or electrocautery), TachoSil® was associated with the decreased air leak duration (WMD: -3.32 days; 95% CI: -5.34--1.31; P = 0.001), chest tube duration (WMD: -1.99 days; 95% CI: -3.14--0.84; P = 0.0007), hospital stay (WMD: -1.89 days; 95% CI: -2.42--1.35; P < 0.0001), and incidence of prolonged air leak (RR: 0.57; 95% CI: 0.35-0.92; P = 0.02). No significant difference was found between the two groups regarding the incidence of postoperative complications (RR: 0.86; 95% CI: 0.69-1.06; P = 0.16). CONCLUSIONS: TachoSil® was safe, cost-effective and superior over standard treatment for patients who underwent pulmonary surgery in decreasing incidence of postoperative air leak, air leak duration, chest tube duration and the length of hospital stay.

External suction versus simple water-seal on chest drainage following pulmonary surgery: an updated meta-analysis.

OBJECTIVES: The decision to apply simple water-seal drainage or the addition of an external suction to the simple water-seal drainage following pulmonary surgery is made based on the surgeon's experience or preference and has remained controversial. This meta-analysis aimed to assess the effects of the addition of suction to simple water-seal on the postoperative outcomes. METHODS: PubMed, EMBASE and Web of Science were searched from their inception to 30 August 2017. The risk ratio and the weight mean difference were calculated for dichotomous and continuous outcomes, respectively, each with 95% confidence intervals (CIs). The heterogeneity and risk of bias were also assessed. RESULTS: A total of 10 randomized controlled trials enrolling 1601 patients were included. Overall, compared with simple water-seal, the addition of external suction reduced the occurrence of postoperative pneumothorax (risk ratio 0.35, 95% CI 0.13-0.93; P = 0.04) and other cardiopulmonary complications (risk ratio 0.65, 95% CI 0.48-0.89; P = 0.008), and increased the duration of chest tube drainage (weight mean difference 0.92 days, 95% CI 0.04-1.81, P = 0.04). However, the effect difference between the 2 groups was not significant regarding air leak duration, length of hospital stay and the occurrence of prolonged air leak. The stability of these studies was strong. No evidence of publication bias was detected. CONCLUSIONS: The addition of suction to simple water-seal made no difference to air leak duration, hospital stay or the occurrence of prolonged air leak following pulmonary surgery. In patients where there is concern about a residual or increasing pneumothorax, the addition of suction may be applied selectively.

Long-term outcomes and prognostic markers in gallbladder cancer.

Cancer-related inflammation and systemic inflammatory markers have been widely recognized as an essential part in tumor multiplication, invasion, and metastasis of tumor cells. This study aimed to estimate and compare the prognostic value of various biomarkers on overall survival (OS) in patients with gallbladder cancer patients.We performed a retrospective study of 159 patients received different therapies in West China Hospital from 2009 to 2014. The preoperative biomarker data, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), lactate dehydrogenase, and alkaline phosphatase, as well as other clinical information, were obtained from electronic record. And the receiver operating characteristic curves were used to analyze the optimal cut-off values of them. Kaplan-Meier survival analysis and Cox proportional hazard model analysis were applied to evaluate the association between markers and OS.The optimal cut-off value was 4.39 for NLR, 181.85 for PLR, 0.30 for MLR, and 3.02 for carcinoembryonic antigen (CEA). Kaplan-Meier analysis and univariate Cox analysis both demonstrated the significant prognostic value of NLR, MLR, and CEA. However, PLR failed to be a significant predictor of OS. The multivariate Cox analysis showed that preoperative NLR and CEA were independent prognostic factors for OS.Advanced tumor/node/metastasis stage, enhanced pretherapeutic NLR, and CEA were significantly associated with worse OS of gallbladder cancer patients. Furthermore, NLR was a better prognostic factor than CEA in advanced T (T3-T4) stage patients, while CEA was better for early T (T1-T2) stage, early N (N0-N1) stage, and early M (M0) stage patients.